Circadian variation of microRNA expression profile in CD133+ progenitor cells

Author(s)

Marina Marçola

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
• Defense date: 2015-01-28

Examining board members

Regina Pekelmann Markus; Ricardo José Giordano; Miriam Galvonas Jasiulionis Leon; Marimelia Aparecida Porcionatto; Wilson Araújo da Silva Junior

• Advisor: Regina Pekelmann Markus

Abstract

The phenotype of primary cells in culture varies according to the donor environmental condition. We have recently shown that the light/dark cycle impose a molecular program that is hereditable in culture. In order to evaluate the molecular mechanisms of cellular memory, here we isolated CD133+ progenitor cells from cremaster muscle explants and investigated whether the expression of microRNAs (miRNAs), could result in different phenotypes according the phase of ligh/dark cycle when cells were obtained. The global miRNA sequencing using SOLiD4 Platform, and analyzed by EdgeR, TargetScan and MetaCore, revealed the expression of a total of 541 mature miRNAs, and two distinct miRNAs signatures according to the hour when cells were obtained. miR-1249 and miR-129-2-3p are more expressed during daytime and favor the maintenance of cellular pluri/multipotency. Nighttime cells express higher amounts of miR-182, miR96-5p, miR-223-3p, miR-146a-3p and miR-146a-5p that inhibit the inflammatory response and favor the cellular maturation when compared to daytime cells. The functional analysis of the inflammatory response inhibition during nighttime was confirmed by PCR array and revealed lower expression level of genes related to TLR/NF-κB pathway, including Traf6, a putative target mRNA of miR-146a. Additionally, the nuclear translocation of NF-κB is reduced in nighttime cells and it is inversely correlated to the nocturnal the plasma level of melatonin. We also showed that melatonin in vitro favors the cellular pluri/multipotency, increasing CD133, miR-1249 and miR-129-2-3p expression. However, this effect depends on cellular context, as the expression of melatonin receptors also shows a daily variation. Altogether, our data suggest that the light/dark cycle interferes on miRNAs expression profile and imposes a rhythmic phenotype variation in CD133+ cells (AU)

• FAPESP's process: 11/01304-8 - Effect of melatonin on the subpopulations of cultured endothilial cells
• Grantee: Marina Marçola Pereira de Freitas
• Support Opportunities: Scholarships in Brazil - Doctorate